Introduction
The genomic landscape of Langerhans cell histiocytosis (LCH) has been
markedly transformed by the identification of variants activating the
mitogen-activated protein kinase (MAPK) pathway, the first and most
common being the BRAF p.V600E mutation. 1In-frame BRAF deletions have subsequently been found in LCH, the
most common being the BRAF p.N486_P490 deletion, which was
recently detected in 19 of 69 (28%) of adults with LCH evaluated by
next generation sequencing (NGS). 2 MAPK pathway
inhibition resulted in remarkable responses, but with rapid reactivation
upon discontinuation of therapy. 3,4 Trametinib, a
MEK1/2 inhibitor, showed impressive activity in an adult patient
reported by Lee et al. 5 Yet, acquired resistance to
trametinib due to MAP2K1 mutations were also recently reported.6 Here we are reporting 3 LCH patients withBRAF p.N486_P490del or MAP2K1 p.K57_G61del who are
responding to trametinib monotherapy.